Details

Autor(en) / Beteiligte

• Guo, Pan
• Chu, Xin
• Wu, Chengjin
• Qiao, Tianjiao
• Guan, Wenli
• Zhou, Chuanzheng
• Wang, Tao
• Tian, Changlin
• He, Gang
• Chen, Gong

Titel

Peptide Stapling by Crosslinking Two Amines with α‐Ketoaldehydes through Diverse Modified Glyoxal‐Lysine Dimer Linkers

Ist Teil von

• Angewandte Chemie, 2024-04, Vol.136 (16), p.n/a

Ort / Verlag

Weinheim: Wiley Subscription Services, Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• α‐Ketoaldehydes play versatile roles in the ubiquitous natural processes of protein glycation. However, leveraging the reactivity of α‐ketoaldehydes for biomedical applications has been challenging. Previously, the reactivity of α‐ketoaldehydes with guanidine has been harnessed to design probes for labeling Arg residues on proteins in an aqueous medium. Herein, a highly effective, broadly applicable, and operationally simple protocol for stapling native peptides by crosslinking two amino groups through diverse imidazolium linkers with various α‐ketoaldehyde reagents is described. The use of hexafluoroisopropanol as a solvent facilitates rapid and clean reactions under mild conditions and enables unique selectivity for Lys over Arg. The naturally occurring GOLD/MOLD linkers have been expanded to encompass a wide range of modified glyoxal‐lysine dimer (OLD) linkers. In a proof‐of‐concept trial, these modular stapling reactions enabled a convenient two‐round strategy to streamline the structure–activity relationship (SAR) study of the wasp venom peptide anoplin, leading to enhanced biological activities. A broadly applicable and operationally simple protocol for stapling native peptides by the crosslinking of two amino groups through diverse imidazolium linkers with various α‐ketoaldehyde reagents has been developed. Except for Cys, all unprotected proteinogenic amino acids are tolerated. The reactivity of Arg side chains can be effectively suppressed. The use of HFIP solvent is the key to achieving high reactivity and selectivity.